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Global Perspective on Locoregional Therapies in HCC

Panelists: Ghassan K. Abou-Alfa, MD, Weill Cornell Medical College; Peter Galle, MD, PhD Johannes Gutenberg University, Mainz; Riad Salem, MD, Northwestern University; Amit Singal, MD UT Southwestern Medical Center
Published: Thursday, Dec 06, 2018



Transcript: 

Ghassan K. Abou-Alfa, MD: We all agree that surgery, resection, and transplant are used with curative intent. Sadly, they are amenable to only a certain number of patients—maybe about 15% or so. As Riad mentioned, patients might present or migrate to a more advanced disease, in which the local therapies will come into play and, of course, systemic therapy will come in a bit later on. As Amit mentioned to us, there is no role yet proven for adjuvant therapy. This is a discussion that has been ongoing for a long time with yttrium andiodine-131, then with sorafenib, and now with checkpoint inhibitors. So far, everything has been negative. However, the current intent is to see if the current trials looking at additional checkpoint inhibitors, like the CheckMate 9DX trial, might lead to a suggestion that the checkpoint inhibitors might be of value, in regard to adjuvant therapy. We don’t know that yet. This sums up where we are in terms of therapy.

Riad already kindly started to discuss embolization. How do you choose radioembolization, chemoembolization, bland embolization? There’s an endless number. Who is who here?

Riad Salem, MD: There’s no doubt that the standard of care for patients who are candidates for embolization is chemoembolization. That’s what we have level 1 evidence on, and that’s sort of what most people follow, particularly in the West and particularly in Asia. The reality is that there are patients who we will individualize to something else, and there is a lot of center expertise. For example, Memorial Sloan Kettering practices bland embolization with similar outcomes. At Northwestern, we practice a lot of yttrium radioembolization, also with similar outcomes. I think the evolution of embolotherapy, while demonstrating a survival difference, is going to be difficult. Things like quality of life, toxicity, and cost are things that are going to be important as we develop new guidelines. The reality is, patients come in to see us, and there are various types of embolotherapy. There are advantages and disadvantages to all of them. Center expertise is very important, just as it is for resection or transplantation. That will often dictate what the patients get. In terms of what the data show, the survival is effectively the same with all of them when you observe the outcomes. There are some differences in tumor response, side-effect profile, and quality of life that I think we really need to study.

Ghassan K. Abou-Alfa, MD: Peter, along that line, who, in your mind-set, would be the right patient for yttrium embolization?

Peter Galle, MD, PhD: Yttrium is a complex story. It’s basically a problem because of the experience of the center, exactly as Riad was saying. Trials have been trying to compare yttrium with sorafenib. We now have 3 phase III trials. They all prove to be negative, but it is quite clear that if you, for example, compare a surgical approach with a drug, all these influences—with respect to operator experience and center experience—will influence or have an impact. It basically means that it’s not the same whether you receive the therapy in Chicago or in some other place. That is really contributing to the difficulty. In my personal experience, I think yttrium plays a role, but the group of patients is undefined. In guidelines we do not have the evidence to clearly point out what can be done. We have the situation where yttrium is applied in the intermediate stage as an alternative to TACE [transcatheter arterial chemoembolization], and Riad has very nicely shown that there is better local tumor control but similar outcome. What does that mean? This is difficult to assess, and I would again follow the experience of a center. If you are very good at it, it’s perfect for the patient. In the advanced stage, if we have to make an individualized decision where we cannot give guidance, it comes back to center experience.

Ghassan K. Abou-Alfa, MD: Fair enough. I think this is an important point. Amit, I’d like to hear your thoughts or criticisms with regard to these studies that Peter referred to. As we know, and this is not to say that you all agree—and maybe there are some nuances in regard to BCLC [Barcelona Clinic Liver Cancer]-B staging—but give or take, BCLC-B patients are the ones who we’re going to apply some local therapy to. As was presented by both Riad and Peter, we have options like chemoembolization, bland embolization, or radioembolization per se. On the other hand, the comparative efforts, for example, were seen with the SARAH study, which was radioembolization versus sorafenib. In other words, you’re comparing a BCLC-B kind of therapy to BCLC-C. There is some kind of push of the Bs to extend more into the Cs or vice versa. Is this the right approach? What are your thoughts on that?

Amit Singal, MD: I think the BCLC system nicely puts people into these buckets—BCLC-B, BCLC-C. At the end of the day, it’s more so a spectrum. As we try to figure out where radioembolization fits, does it fit into 1 bucket cleanly or can it be extended to several of these buckets? I think SARAH and SIRveNIB started to look at this. I don’t think it’s the end of this discussion. We all know that there are some limitations to this. For example, both of the studies used SIR-Spheres, not TheraSpheres. And so, you can imagine that with more boosting and higher-radiation doses within the tumor you may have differential responses. And the results of the trials may be different. I think what we can say is based on these data; we have no data to say that Y-90 [yttrium-90] performs better than sorafenib. And so, systemic therapy remains, at least in my mind, the current standard of care for BCLC patients, including those with portal vein involvement.

However, we also have some nonrandomized data that show that you can have good results with TheraSpheres in selected patients. That’s why I don’t think this is the end of the story. I think we’re only halfway through. We need to continue with trials to really figure out where TheraSpheres or Y-90 fit into this whole story.

Transcript Edited for Clarity 

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Transcript: 

Ghassan K. Abou-Alfa, MD: We all agree that surgery, resection, and transplant are used with curative intent. Sadly, they are amenable to only a certain number of patients—maybe about 15% or so. As Riad mentioned, patients might present or migrate to a more advanced disease, in which the local therapies will come into play and, of course, systemic therapy will come in a bit later on. As Amit mentioned to us, there is no role yet proven for adjuvant therapy. This is a discussion that has been ongoing for a long time with yttrium andiodine-131, then with sorafenib, and now with checkpoint inhibitors. So far, everything has been negative. However, the current intent is to see if the current trials looking at additional checkpoint inhibitors, like the CheckMate 9DX trial, might lead to a suggestion that the checkpoint inhibitors might be of value, in regard to adjuvant therapy. We don’t know that yet. This sums up where we are in terms of therapy.

Riad already kindly started to discuss embolization. How do you choose radioembolization, chemoembolization, bland embolization? There’s an endless number. Who is who here?

Riad Salem, MD: There’s no doubt that the standard of care for patients who are candidates for embolization is chemoembolization. That’s what we have level 1 evidence on, and that’s sort of what most people follow, particularly in the West and particularly in Asia. The reality is that there are patients who we will individualize to something else, and there is a lot of center expertise. For example, Memorial Sloan Kettering practices bland embolization with similar outcomes. At Northwestern, we practice a lot of yttrium radioembolization, also with similar outcomes. I think the evolution of embolotherapy, while demonstrating a survival difference, is going to be difficult. Things like quality of life, toxicity, and cost are things that are going to be important as we develop new guidelines. The reality is, patients come in to see us, and there are various types of embolotherapy. There are advantages and disadvantages to all of them. Center expertise is very important, just as it is for resection or transplantation. That will often dictate what the patients get. In terms of what the data show, the survival is effectively the same with all of them when you observe the outcomes. There are some differences in tumor response, side-effect profile, and quality of life that I think we really need to study.

Ghassan K. Abou-Alfa, MD: Peter, along that line, who, in your mind-set, would be the right patient for yttrium embolization?

Peter Galle, MD, PhD: Yttrium is a complex story. It’s basically a problem because of the experience of the center, exactly as Riad was saying. Trials have been trying to compare yttrium with sorafenib. We now have 3 phase III trials. They all prove to be negative, but it is quite clear that if you, for example, compare a surgical approach with a drug, all these influences—with respect to operator experience and center experience—will influence or have an impact. It basically means that it’s not the same whether you receive the therapy in Chicago or in some other place. That is really contributing to the difficulty. In my personal experience, I think yttrium plays a role, but the group of patients is undefined. In guidelines we do not have the evidence to clearly point out what can be done. We have the situation where yttrium is applied in the intermediate stage as an alternative to TACE [transcatheter arterial chemoembolization], and Riad has very nicely shown that there is better local tumor control but similar outcome. What does that mean? This is difficult to assess, and I would again follow the experience of a center. If you are very good at it, it’s perfect for the patient. In the advanced stage, if we have to make an individualized decision where we cannot give guidance, it comes back to center experience.

Ghassan K. Abou-Alfa, MD: Fair enough. I think this is an important point. Amit, I’d like to hear your thoughts or criticisms with regard to these studies that Peter referred to. As we know, and this is not to say that you all agree—and maybe there are some nuances in regard to BCLC [Barcelona Clinic Liver Cancer]-B staging—but give or take, BCLC-B patients are the ones who we’re going to apply some local therapy to. As was presented by both Riad and Peter, we have options like chemoembolization, bland embolization, or radioembolization per se. On the other hand, the comparative efforts, for example, were seen with the SARAH study, which was radioembolization versus sorafenib. In other words, you’re comparing a BCLC-B kind of therapy to BCLC-C. There is some kind of push of the Bs to extend more into the Cs or vice versa. Is this the right approach? What are your thoughts on that?

Amit Singal, MD: I think the BCLC system nicely puts people into these buckets—BCLC-B, BCLC-C. At the end of the day, it’s more so a spectrum. As we try to figure out where radioembolization fits, does it fit into 1 bucket cleanly or can it be extended to several of these buckets? I think SARAH and SIRveNIB started to look at this. I don’t think it’s the end of this discussion. We all know that there are some limitations to this. For example, both of the studies used SIR-Spheres, not TheraSpheres. And so, you can imagine that with more boosting and higher-radiation doses within the tumor you may have differential responses. And the results of the trials may be different. I think what we can say is based on these data; we have no data to say that Y-90 [yttrium-90] performs better than sorafenib. And so, systemic therapy remains, at least in my mind, the current standard of care for BCLC patients, including those with portal vein involvement.

However, we also have some nonrandomized data that show that you can have good results with TheraSpheres in selected patients. That’s why I don’t think this is the end of the story. I think we’re only halfway through. We need to continue with trials to really figure out where TheraSpheres or Y-90 fit into this whole story.

Transcript Edited for Clarity 
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